The goal of this research is to examine the effects of bone morphogenetic protein-5 (BMP-5) during skeletal growth. Understanding the in vivo role of BMP-5 will allow these growth factors to be considered for osteoporosis treatment and therapy. Long bone functional adaptation and regeneration will be examined in the short ear mouse and its control litter mates in a pair of experimental studies. This animal model has a deletion for the BMP-5 gene. Both sets of experiments are designed to evaluate the short and long-term bone tissue responses in the short ear mouse and age-matched controls. These studies combine to enhance our understanding of the mechanisms of action of BMPs in bone growth, adaptation and regeneration. In the first set of experiments, the role of BMP-5 in mechanically- regulated functional adaptation will be studied following hindlimb suspension and suspension followed by reloading. Unloading during hindlimb suspension will be quantified using in vivo strain gages. Femoral structural, geometric and material properties will be examined for genetic effects on the adaptational response. With the experimental data, previously-developed analytical models of long bone growth and development will be refined and expanded to include non-mechanical effects. The second set of experiments will examine the role of BMP-5 in fracture healing. Standard closed fractures of the femoral diaphysis will be created. Short-term tissue response will be quantified histologically during the first two weeks post-fracture, and long-term biomechanical integrity of the healing femur will be evaluated during the first five weeks following fracture.